Alteration in NMDA Receptor Mediated Glutamatergic Neurotransmission in the Hippocampus During Senescence

Glutamate is the primary excitatory neurotransmitter in neurons and glia. N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate receptors are major ionotropic glutamate receptors. Glutamatergic neurotransmission is strongly linked with Ca²⁺ homeostasis. Research has provided ample evidence that brain aging is associated with altered glutamatergic neurotransmission and Ca²⁺ dysregulation. Much of the work has focused on the hippocampus, a brain region critically involved in learning and memory, which is particularly susceptible to dysfunction during senescence. The current review examines Ca²⁺ regulation with a focus on the NMDA receptors in the hippocampus. Integrating the knowledge of the complexity of age-related alterations in Ca²⁺ homeostasis and NMDA receptor-mediated glutamatergic neurotransmission will positively shape the development of highly effective therapeutics to treat brain disorders including cognitive impairment.